2014-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/690206摘要：生物製劑是由生命系統或生物體所製造的藥品或醫療器材。許多重要可救命但也昂貴生物製劑的專利即將於未來幾年到期，這可提供世界上或台灣的藥廠製造生物製劑學名藥的契機。生物製劑的學名藥又稱為生物相似性藥品，生物相似性藥品與原廠對照生物製劑是具有高度的相似性，雖然在臨床非活性成份上僅有微小的差異，但是在安全性、純度及效力上無臨床上有意義的差別。雖美國、歐盟及我國已公告生物相似性產品的核准的準則，但這些準則並未提供評估及核准生物相似產品上市之品質的指標及其相對統計推論的理論與方法。為了要降低成本及造福病人的目的，生物相似性藥品的研發不能採用原廠對照生物製劑同樣傳統新藥的研發規模。為了要達到此一目的，我們可用統計方法縮短生物相似性產品研發的過程。本計畫為三年計畫並包括三部份:第一部份為應用平行線生物檢定法於生物相似性藥品之設限資料的對等性之評估。第二部份為應用多變量對等性觀念，訂定交替性及轉換性的評估指標及其相對應的統計推論。第三部份我們建議以個體與處理交互作用的變異數為評估互換性的指標，並將推導其相對應的統計方法，我們將執行模擬研究，使用經驗型Ｉ誤差機率及檢定力，評估所提出的方法，並用數例介紹所提出方法之應用。<br> Abstract: Biological drug products are therapeutic moiety manufactured by a living system or organisms. Most of life-saving but yet expensive biological products will lose their patents in the next few years. This provides the opportunity for other drug manufacturers including some in Taiwan to produce the generic versions of biological products, referred to as biosimilar products or follow-on biologics. Biosimilar drug products mean that the biological product is highly similar to the reference product notwithstanding minor differences in clinical inactive components and that there are no clinically meaningful differences between the biological product and reference product in terms of the safety, purity and potency of the product. Although most of countries such as the United States, the European Medical Agency, or Taiwan have issues several guidelines to approve biosimilar drug products, the criteria and statistical theory and methodology have not been developed to assess the quality of biosimilar products as compared to the innovator’s product, For development of statistical theory and methods for evaluation of biosimilar products, it is crucial and imperative that the full scale of new drug development be avoided to cut down the cost for development of biosimilar drug products to benefit the patients with unmet medical need. To achieve these goals, this three-year project consists of three parts: The first part is to apply the parallel line assay to evaluation of biosimilar drug products based on censored endpoints. The second part is to develop the criteria for alternating and switching in terms of multivariate bioequivalence and to derive statistical methods for evaluation of multivariate bioequivalence. The last part proposes the variance of the subject-by-formulation interaction as a criterion for evaluation of interchangeability and will derive procedures for the inference for interchangeability. We will also report the results of simulation studies to evaluate the performance, in terms of size and power, of our proposed methods. Numerical examples are presented to illustrate the suggested procedures.生物相似性藥品生物相似性互換性交替性轉換性Biosimilar drug productBiosimilarityInterchangeabilityAlternatingSwitching